Are there differences in clinical presentation, radiologic findings, and outcomes in female patients with cavernous malformation?

Background: Little data exist regarding sex differences in cavernous malformations (CM) patients. Methods: From an ongoing, prospective registry of consenting adults with CM, we assessed the differences between male and female patients in regard to age at presentation, type of presentation, radiologic characteristics and prospective, symptomatic hemorrhage and or focal neurologic deficit (FND) risk and functional outcome. Cox proportional-hazard ratios and 95% confidence intervals with P values < 0.05 were considered significant in the outcome analysis. Familial form CM female patients were compared to sporadic form. Results: As of 1/1/2023, our cohort comprised 386 people (58.0% female) after excluding radiation-induced CM. There were no demographic or clinical presentation differences between male and female patients. Radiological features did not differ between sexes, except that female, sporadic patients were more likely to have an associated developmental venous anomaly (DVA) (43.2% male vs. 56.2% female; p = 0.03). Overall, there was no difference in prospective symptomatic hemorrhage or functional outcome between sexes. Female sex was a predictor of symptomatic hemorrhage or FND in sporadic patients with ruptured CM (39.6% males versus 65.7% females; p = 0.02). The latter was not due to presence or absence of DVA. Familial CM females were more likely to have a spinal cord CM (15.2% familial female vs. 3.9% sporadic female; p = 0.001) and had a longer time to recurrent hemorrhage than sporadic female (2.2 years sporadic vs. 8.2 years familial; p = 0.0006). Conclusion: Minimal differences in clinical, radiologic, and outcomes were found in male versus female patients and familial versus sporadic females in the overall CM patient group. The finding that sporadic form female patients with history of prior hemorrhage had increased rates of prospective hemorrhage or FND compared to male patients raise the question whether to “lump” or “split” ruptured versus unruptured CM patients when analyzing risk factors for prospective hemorrhage in natural history studies.